A "Candidate-Interactome" Aggregate Analysis of Genome-Wide Association Data in Multiple Sclerosis

Though difficult, the study of gene-environment interactions in multifactorial diseases is crucial for interpreting the relevance of non-heritable factors and prevents from overlooking genetic associations with small but measurable effects. We propose a "candidate interactome" (i.e. a group of genes whose products are known to physically interact with environmental factors that may be relevant for disease pathogenesis) analysis of genome-wide association data in multiple sclerosis. We looked for statistical enrichment of associations among interactomes that, at the current state of knowledge, may be representative of gene-environment interactions of potential, uncertain or unlikely relevance for multiple sclerosis pathogenesis: Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, HHV8-Kaposi sarcoma, H1N1-influenza, JC virus, human innate immunity interactome for type I interferon, autoimmune regulator, vitamin D receptor, aryl hydrocarbon receptor and a panel of proteins targeted by 70 innate immune-modulating viral open reading frames from 30 viral species. Interactomes were either obtained from the literature or were manually curated. The P values of all single nucleotide polymorphism mapping to a given interactome were obtained from the last genome-wide association study of the International Multiple Sclerosis Genetics Consortium & the Wellcome Trust Case Control Consortium, 2. The interaction between genotype and Epstein Barr virus emerges as relevant for multiple sclerosis etiology. However, in line with recent data on the coexistence of common and unique strategies used by viruses to perturb the human molecular system, also other viruses have a similar potential, though probably less relevant in epidemiological terms. © 2013 Mechelli et al.

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis. © 2011 Macmillan Publishers Limited. All rights reserved.

Investigation of the effect of balconies on natural ventilation of dwellings in high-rise residential buildings in subtropical climate

Balconies, as one of the main architectural features in subtropical climates, are assumed to enhance the ventilation performance of buildings by redirecting the wind. Although there are some studies on the effect of balconies on natural ventilation inside buildings, the majority have been conducted on single zone buildings with simple geometries. The purpose of this study is to explore the effect of balconies on the internal air flow pattern and ventilation performance of multi-storey residential buildings with internal partitions. To this end, a sample residential unit was selected for investigation and three different conditions tested, base case (no balcony), an open balcony and a semi-enclosed balcony. Computational Fluid Dynamics is used as an analysis method due to its accuracy and ability to provide detailed results. The cases are analysed in terms of average velocity, flow uniformity and number of Air Changes per Hour (ACH). The results suggest the introduction of a semi-enclosed balcony into high-rise dwellings improves the average velocity and flow uniformity. Integrating an open balcony results in reduction of the aforementioned parameters at 0° wind incidence.

Subtypes of psychotic-like experiences are differentially associated with suicidal ideation, plans and attempts in young adults

Psychotic-like experiences (PLEs) have been associated with increased risk of suicidality, but it is unclear whether the level of risk varies with different types of PLE. A cross-sectional online survey was completed by 1610 university students. Respondents completed the Community Assessment of Psychic Experiences-15 (CAPE-P15) assessing PLEs on three subscales: Perceptual Abnormalities (PA), Persecutory Ideation (PI) and Bizarre Experiences (BE). Lifetime suicidal ideation, plans and attempts, cannabis, ecstasy and methamphetamine use and family history of mental disorder were also assessed. Multinomal logistic regression was used to examine unique determinants of lifetime suicidality, defined as any history of (i) suicidal ideation or plans and (ii) any attempt, relative to no lifetime history of suicidality. A lifetime history of PA and PI provided significant unique contributions to the prediction of suicide risk, after control for other significant predictors. BE were not associated with any suicide variable demonstrating the variation in risk of suicidality with different types of PLEs. Perceptual abnormalities and persecutory ideation as measured by the CAPE-P15 are the PLEs associated with a higher risk of lifetime suicidality.

Current CAPE-15: A measure of recent psychotic-like experiences and associated distress

Aim Psychotic-like experiences (PLEs) are common in young people and are associated with both distress and adverse outcomes. The Community Assessment of Psychic Experiences-Positive Scale (CAPE-P) provides a 20-item measure of lifetime PLEs. A 15-item revision of this scale was recently published (CAPE-P15). Although the CAPE-P has been used to assess PLEs in the last 12 months, there is no version of the CAPE for assessing more recent PLEs (e.g. 3 months). This study aimed to determine the reliability and validity of the current CAPE-P15 and assess its relationship with current distress. Method A cross-sectional online survey of 489 university students (17–25 years) assessed lifetime and current substance use, current distress, and lifetime and 3-month PLEs on the CAPE-P15. Results Confirmatory factor analysis indicated that the current CAPE-P15 retained the same three-factor structure as the lifetime version consisting of persecutory ideation, bizarre experiences and perceptual abnormalities. The total score of the current version was lower than the lifetime version, but the two were strongly correlated (r = .64). The current version was highly predictive of generalized distress (r = .52) and indices that combined symptom frequency with associated distress did not confer greater predictive power than frequency alone. Conclusion This study provided preliminary data that the current CAPE-P15 provides a valid and reliable measure of current PLEs. The current CAPE-P15 is likely to have substantial practical utility if it is later shown to be sensitive to change, especially in prevention and early intervention for mental disorders in young people.

Abstract concepts made real: A pilot study examining pedagogical approaches in thermodynamics tutorials

BACKGROUND OR CONTEXT Thermodynamics is a core concept for mechanical engineers yet notoriously difficult. Evidence suggests students struggle to understand and apply the core fundamental concepts of thermodynamics with analysis indicating a problem with student learning/engagement. A contributing factor is that thermodynamics is a ‘science involving concepts based on experiments’ (Mayhew 1990) with subject matter that cannot be completely defined a priori. To succeed, students must engage in a deep-holistic approach while taking ownership of their learning. The difficulty in achieving this often manifests itself in students ‘not getting’ the principles and declaring thermodynamics ‘hard’. PURPOSE OR GOAL Traditionally, students practice and “learn” the application of thermodynamics in their tutorials, however these do not consider prior conceptions (Holman & Pilling 2004). As ‘hands on’ learning is the desired outcome of tutorials it is pertinent to study methods of improving their efficacy. Within the Australian context, the format of thermodynamics tutorials has remained relatively unchanged over the decades, relying anecdotally on a primarily didactic pedagogical approach. Such approaches are not conducive to deep learning (Ramsden 2003) with students often disengaged from the learning process. Evidence suggests (Haglund & Jeppsson 2012), however, that a deeper level and ownership of learning can be achieved using a more constructivist approach for example through self generated analogies. This pilot study aimed to collect data to support the hypothesis that the ‘difficulty’ of thermodynamics is associated with the pedagogical approach of tutorials rather than actual difficulty in subject content or deficiency in students. APPROACH Successful application of thermodynamic principles requires solid knowledge of the core concepts. Typically, tutorial sessions guide students in this application. However, a lack of deep and comprehensive understanding can lead to student confusion in the applications resulting in the learning of the ‘process’ of application without understanding ‘why’. The aim of this study was to gain empirical data on student learning of both concepts and application, within thermodynamic tutorials. The approach taken for data collection and analysis was: - 1 Four concurrent tutorial streams were timetabled to examine student engagement/learning in traditional ‘didactic’ (3 weeks) and non-traditional (3 weeks). In each week, two of the selected four sessions were traditional and two non-traditional. This provided a control group for each week. - 2 The non-traditional tutorials involved activities designed to promote student-centered deep learning. Specific pedagogies employed were: self-generated analogies, constructivist, peer-to-peer learning, inquiry based learning, ownership of learning and active learning. - 3 After a three-week period, teaching styles of the selected groups was switched, to allow each group to experience both approaches with the same tutor. This also acted to mimimise any influence of tutor personality / style on the data. - 4 At the conclusion of the trial participants completed a ‘5 minute essay’ on how they liked the sessions, a small questionnaire, modelled on the modified (Christo & Hoang, 2013)SPQ designed by Biggs (1987) and a small formative quiz to gauge the level of learning achieved. DISCUSSION Preliminary results indicate that overall students respond positively to in class demonstrations (inquiry based learning), and active learning activities. Within the active learning exercises, the current data suggests students preferred individual rather than group or peer-to-peer activities. Preliminary results from the open-ended questions such as “What did you like most/least about this tutorial” and “do you have other comments on how this tutorial could better facilitate your learning”, however, indicated polarising views on the nontraditional tutorial. Some student’s responded that they really like the format and emphasis on understanding the concepts, while others were very vocal that that ‘hated’ the style and just wanted the solutions to be presented by the tutor. RECOMMENDATIONS/IMPLICATIONS/CONCLUSION Preliminary results indicated a mixed, but overall positive response by students with more collaborative tutorials employing tasks promoting inquiry based, peer-to-peer, active, and ownership of learning activities. Preliminary results from student feedback supports evidence that students learn differently, and running tutorials focusing on only one pedagogical approached (typically didactic) may not be beneficial to all students. Further, preliminary data suggests that the learning / teaching style of both students and tutor are important to promoting deep learning in students. Data collection is still ongoing and scheduled for completion at the end of First Semester (Australian academic calendar). The final paper will examine in more detail the results and analysis of this project.

Methodology for developing competency standards for dietitians in Australia

Competency standards document the knowledge, skills, and attitudes required for competent performance. This study develops competency standards for dietitians in order to substantiate an approach to competency standard development. Focus groups explored the current and emerging purpose, role, and function of the profession, which were used to draft competency standards. Consensus was then sought using two rounds of a Delphi survey. Seven focus groups were conducted with 28 participants (15 employers/practitioners, 5 academics, 8 new graduates). Eighty-two of 110 invited experts participated in round one and 67 experts completed round two. Four major functions of dietitians were identified: being a professional, influencing the health of individuals, groups, communities, and populations through evidence-based nutrition practice, and working collaboratively in teams. Overall there was a high level of consensus on the standards: 93% achieved agreement by participants in round one and all revised standards achieved consensus on round 2. The methodology provides a framework for other professions wishing to embark on competency standard review or development.

What do prisoners eat? Nutrient intakes and food practices in a high secure prison

There are limited studies on the adequacy of prisoner diet and food practices, yet understanding these are important to inform food provision and assure duty of care for this group. The aim of this research was to assess the dietary intakes of prisoners to inform food and nutrition policy in this setting. This research used a cross-sectional design with convenience sampling in a 945 bed male high secure prison. Multiple methods were used to assess food available at the group level, including verification of food portion, quality, and practices. A pictorial tool supported the diet history method. Of 276 eligible prisoners, 120 dietary interviews were conducted and verified against prison records, with 106 deemed plausible. The results showed the planned food to be nutritionally adequate, with the exception of vitamin D for older males and long chain fatty acids, with sodium above Upper Limits. The Australian Dietary Targets for chronic disease risk were not achieved. High energy intakes were reported with median 13.8MJ (SE 0.3MJ). Probability estimates of inadequate intake varied with age groups: magnesium 8% (>30 years), 2.9% (<30 years); calcium 6.0% (>70 years), 1.5% (<70 years); folate 3.5%; zinc and iodine 2.7%; and vitamin A 2.3%. Nutrient intakes were greatly impacted by self-funded snacks. Results suggest nutrient intakes nutritionally favourable when compared to males in the community. This study highlights the complexity of food provision in the prison environment, and also poses questions for population level dietary guidance in delivering appropriate nutrients within energy limits.

The prevalence and correlates of childhood trauma in patients with early psychosis

Objective: To describe the prevalence and demographic, clinical and functional correlates of childhood trauma in patients attending early psychosis clinics. Method: Participants were recruited from outpatients attending four early psychosis services. Exposure to childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ). Psychopathology was measured using the Positive and Negative Syndrome Scale and the Depression, Anxiety and Stress Scale. Social and vocational functioning and substance use were also assessed. Results: Over three-quarters of the 100 patients reported exposure to any childhood trauma. Emotional, physical and sexual abuse were reported by 54%, 23% and 28% of patients, respectively, while 49% and 42% of patients reported emotional and physical neglect, respectively. Female participants were significantly more likely to be exposed to emotional and sexual abuse. Exposure to childhood trauma was correlated with positive psychotic symptoms and higher levels of depressive, anxiety and stress symptoms; however, it had no impact on social or vocational functioning or recent substance use. Conclusion: Exposure to childhood trauma was common in patients with early psychosis, and associated with increased symptomatology. Existing recommendations that standard clinical assessment of patients with early psychosis should include inquiry into exposure to childhood trauma are supported.

Caprate: un sistema de interpretación de problemas en lenguaje natural

199 p.

The equivalent conductance of solutions of picric acid

Picric acid possesses the property, which is rare among strong electrolytes, of having a convenient distribution ratio between water and certain organic solvents such as benzene, chloroform, etc. Because of this property, picric acid offers peculiar advantages for studying the well known deviations of strong electrolytes from the law of mass action, for; by means of distribution experiments, the activities of picric acid in various aqueous solutions may be compared.

In order to interpret the results of such distribution experiments, it is necessary to know the degree of ionization of picric acid in aqueous solutions.

At least three series of determinations of the equivalent conductance of picric acid have been published, but the results are not concordant; and therefore, the degree of ionization cannot be calculated with any degree of certainty.

The object of the present investigation was to redetermine the conductance of picric acid solutions in order to obtain satisfactory data from which the degrees of ionization of its solutions might be calculated.

La historia a través del cine. Estados Unidos: una mirada a su imaginario colectivo

Índice: - Glory (1989): una visión dramatizada sobre el origen de los Buffalo Soldiers (Óscar Álvarez Gila). - Los violentos años veinte: gánsters, prohibición y cambios socio-políticos en el primer tercio del siglo xx en Estados Unidos (Aurora Bosch). - La crisis de la democracia en América: Caballero sin espada (Frank Capra, 1939) (José-Vidal Pelaz López). - El manantial, una apología del individualismo norteamericano (José Luis Sánchez Noriega). - Cine y elecciones: El candidato como paradigma del género (Carlos Flores Juberías). - La diplomacia atómica en la Guerra Fría y Estados Unidos: ¿Teléfono rojo? Volamos hacia Moscú (Coro Rubio Pobes). - My Family (Mi familia) (Mario P. Díaz Barrado). - Lars von Trier y Bailar en la oscuridad: ¿lo hemos visto todo ya en el cine? (Iratxe Fresneda). - Estados Unidos: un recorrido por su historia a través del cine de ficción (Coro Rubio Pobes).

Ídolos-espátulas del País Vasco: fabricación, cronología y paralelos

[ES] La industria ósea postpaleolítica, por lo general, pocas veces ha merecido la atención que se le ha concedido a la fabricada durante el Paleolítico Superior. No obstante una de dichas excepciones serán los denominados ídolos-espátulas con decoración acanalada en su mitad proximal, trabajados sobre tibias de "Capra/Ovis" y procedentes por lo que hasta ahora conocemos de contextos sepulcrales megalíticos. En su morfología deben de señalarse el extremo activo romo, al modo de otras espátulas tan comunes en contextos neolíticos, y el extremo proximal decorado con profundos acanalamientos que conforman motivos geométricos más o menos complejos (espiral, zig-zag, etc.) en unos casos y en menos alguna figura antropomorfa femenina. Los primeros hallazgos se realizaron en la provincia de Álava durante la década de los sesenta, destacando entre ellos los procedentes del sepulcro de corredor de San Martín (Laguardia), a los que se sucedieron otros como los de Kurtzebide, Los Llanos, etc. en el mismo territorio y los importantes conjuntos hallados en distintas provincias de la Meseta Norte y en La Rioja. Todos ellos debido al tipo de contexto del que proceden y las características de los ídolos-espátula ritual dan cierto grado de homogeneidad ideológico o religioso a todo el territorio. No obstante, fuera de este territorio y muy alejados desde el punto de vista geográfico existen otros ejemplares (Tell Halula -Siria-, Sesklo, Agios Petras -Grecia-) que muestran gran similitud tipológica aunque no un nexo de unión entre ambas zonas. Por otra parte, hay que subrayar la notable mayor antigüedad del foco oriental y que el contexto del que proceden no es funerario como en el caso de los ejemplares occidentales.

Phylogenomic study of the subfamily Caprinae by cross-species chromosome painting with Chinese muntjac paints

Chromosomal homologies have been established between the Chinese muntjac (Muntiacus reevesi, MRE, 2n = 46) and five ovine species: wild goat (Capra aegagrus, CAE, 2n = 60), argall (Ovis ammon, OAM, 2n = 56), snow sheep (Ovis nivicola, ONI, 2n = 52), red goral (Naemorhedus cranbrooki, NCR, 2n = 56) and Sumatra serow (Capricornis sumatraensis, CSU, 2n = 48) by chromosome painting with a set of chromosome-specific probes of the Chinese muntjac. In total, twenty-two Chinese muntjac autosomal painting probes detected thirty-five homologous segments in the genome of each species. The chromosome X probe hybridized to the whole X chromosomes of all ovine species while the chromosome Y probe gave no signal. Our results demonstrate that almost all homologous segments defined by comparative painting show a high degree of conservation in G-banding patterns and that each speciation event is accompanied by specific chromosomal rearrangements. The combined analysis of our results and previous cytogenetic and molecular systematic results enables us to map the chromosomal rearrangements onto a phylogenetic tree, thus providing new insights into the karyotypic evolution of these species.

贵州四个山羊品种mtDNA多态性及起源分化

采用15种限制性内切酶,研究贵州省4个山羊(capra sp.)品种共93只个体的线粒体DNA多态性。其中BamHI、HindIII和SalI3种酶的酶切类型存在多态。共检测到18种限制性态型,归结为3种mtDNA单倍型。单倍型I和II在贵州山羊4个品种中分布频率较高,分别为77.42%和21.50%,单倍型III分布频率较低(1.08%);品种间亲缘关系聚类分析表明白山羊和黑山羊亲缘关系最近,其次为黔北麻羊,而与小香羊的亲缘关系最远。